Synthesis of oxygenated oleanolic and ursolic acid derivatives with anti-inflammatory properties
| Autor: | Karin R. Claussen, Lisa Tremmel, Andrew M. Camelio, Andrew T. Nelson, Jiyoon Cho, Dionicio Siegel, John DiGiovanni |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Mouse
Clinical Biochemistry Inbred Strains Anti-Inflammatory Agents Molecular Conformation Pharmaceutical Science Biochemistry chemistry.chemical_compound Mice Synthesis Triterpene Drug Discovery Oleanolic acid Skin Cancer chemistry.chemical_classification Chemistry Anti-Inflammatory Agents Non-Steroidal Skin inflammation Pharmacology and Pharmaceutical Sciences Corosolic acid Molecular Medicine Cytokines Female Non-Steroidal medicine.drug_class Stereochemistry 3-epi-Corosolic acid Medicinal & Biomolecular Chemistry 3-epi-Maslinic acid Mice Inbred Strains Chemoprevention Anti-inflammatory Article Natural product Medicinal and Biomolecular Chemistry Ursolic acid Maslinic acid medicine Animals Oleanolic Acid Molecular Biology Oleanane Prevention Organic Chemistry Triterpenes Oxygen |
| Zdroj: | Bioorganic & medicinal chemistry letters, vol 25, iss 19 |
| Popis: | The scalable syntheses of four oxygenated triterpenes have been implemented to access substantial quantities of maslinic acid, 3-epi-maslinic acid, corosolic acid, and 3-epi-corosolic acid. Semi-syntheses proceed starting from the natural products oleanolic acid and ursolic acid. Proceeding over five steps, each of the four compounds can be synthesized on the gram scale. Divergent diastereoselective reductions of α-hydroxy ketones provided access to the four targeted diol containing compounds from two precursors of the oleanane or ursane lineage. These compounds were subsequently evaluated for their ability to inhibit inflammatory gene expression in a mouse model of chemically induced skin inflammation. All compounds possessed the ability to inhibit the expression of one or more inflammatory genes induced by 12-O-tetradecanoylphorbol-13 acetate in mouse skin, however, three of the compounds, corosolic acid, 3-epi-corosolic acid and maslinic acid were more effective than the others. The availability of gram quantities will allow further testing of these compounds for potential anti-inflammatory activities as well as cancer chemopreventive activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|